ES2351295T3 - PRODUCTS TO PREVENT SKIN PENETRATION. - Google Patents

Abstract

The present invention relates to novel cosmetic and/or dermatological compounds and compositions for the photoprotection of human skin and/or hair against the damaging effects of UV radiation, in particular solar radiation. In another embodiment the invention relates to compositions and compounds for topical application comprising at least one photoprotective compound for topical application comprising of hydroxylated derivatives of natural Jojoba wax/oil or its synthetic substitute, esterified with carboxylic acids or aminoacids bearing UV-absorbing groups.

Description

FIELD OF THE INVENTION

The present invention relates to new cosmetic and / or dermatological compounds and compositions for the photoprotection of the skin and / or hair of human beings against the harmful effects of UV radiation, in particular solar radiation. Compositions and compounds for topical application are described which comprise at least one photoprotective compound comprised of hydroxylated derivatives of natural jojoba wax / oil or its synthetic substitute, esterified with carboxylic acids or amino acids having UV absorbing groups, as well as esters of jojoba obtained by transesterification of said wax / oil with alcohols having one or more UV absorber groups. BACKGROUND OF THE INVENTION

During the last two decades, the problem of skin photoprotection has attracted increasing attention. It has become clear that exposure to sunlight can cause not only erythema, photoallergy and photoaging of the skin, but can also damage the skin's immune system and induce or increase the likelihood of malignant transformations. These hazards are probably reinforced by the recently observed decrease in stratospheric ozone levels that cause an increase in UV radiation at ground level.

Due to these considerations, as well as for commercial reasons, the development and production of sunscreen formulations has become an ever growing field of activity.

Many of the existing sunscreen formulations are based on the use of benzophenones and methoxycinnamic acid derivatives. Although these synthetic chemicals are effective UV absorbers, their protective action is relatively short. Being small organic molecules with a molecular mass of <300 Da, they partially penetrate the deepest regions of the epidermis, where they can have adverse reactions, such as the suppression of the skin's immune system. Some of them may have estrogenic effects.

These anti-solar or sunscreen compositions are usually in the form of an oil-in-water emulsion (specifically, a cosmetically acceptable carrier comprising a continuous aqueous dispersion phase and a discontinuous oil dispersed phase) containing, in various concentrations, one or more lipophilic and / or hydrophilic organic filter agents that are capable of selectively absorbing harmful UV radiation, these filter agents (and their amounts) being selected based on the desired protection factor (the protection factor (FP) being expressed mathematically by the ratio of the radiation time required to reach the erythema formation threshold with the UV filter agent with respect to the time required to reach the erythema formation threshold without the UV filter agent).

US 5,547,659 discloses certain topical compositions that have improved efficiency, such as improved sunscreen efficiency to protect the skin from the harmful effects of ultraviolet radiation, such as sunburn and premature aging of the induced skin. for the Sun.

US 4,749,517 discloses an ethoxylated jojoba oil and a process for producing ethoxylated jojoba oil comprising the steps of: (a) hydroxylating jojoba oil by reacting said oil with formic acid and hydrogen peroxide to produce an oil of hydroxylated jojoba; and (b) ethoxylating said hydroxylated jojoba oil by reacting said hydroxylated jojoba oil with ethylene oxide.

Therefore, it will be very advantageous to develop long-lasting non-penetrating photoprotectors limited to stratum corneum, based on natural products. SUMMARY OF THE INVENTION

A photoprotective compound for topical application may comprise hydroxylated derivatives of natural jojoba wax / oil or its synthetic substitute, esterified with carboxylic acids or amino acids having UV absorbing groups.

A tanning compound for topical application may comprise hydroxylated derivatives of natural jojoba wax / oil or its synthetic substitute, esterified with carboxylic acids or amino acids for tanning.

Therefore, in a first aspect, the invention relates to a compound represented by the general formula (I)

CH3 (CH2) mCH (OX) (CH2) nCOO (CH2) iCH (OX) (CH2) kCH3

in which X is an organic group that absorbs light in the ultraviolet region and (CH2) i, (CH2) k,

(CH2) m and (CH2) n are aliphatic chains containing 5 to 30 methylene groups.

The compound of formula (I) may be di (4-methoxycinnamoyl) jojobadiol.

In another aspect, the invention relates to a compound represented by the general formula (II)

CH3 (CH2) mCH (OX) CH (OX) (CH2) nCOO (CH2) iCH (OX) CH (OX) (CH2) kCH3

in which X is an organic group that absorbs light in the ultraviolet region and (CH2) i, (CH2) k,

(CH2) m and (CH2) n are aliphatic chains containing 5 to 30 methylene groups.

The compound of formula (II) may be (4-methoxycinnamoyl) jojobatetraol.

A process for preparing di (4-methoxycinnamoyl) jojobadiol may comprise the step of esterification of jojobadiol with p-cinnamoyl chloride, thereby obtaining

di (4-methoxycinnamoyl) jojobadiol.

A process for preparing tetra (4-methoxycinnamoyl) jojobatetraol may comprise the step of esterification of jojobatetraol with p-cinnamoyl chloride, thereby obtaining (4-methoxycinnamoyl) jojobatetraol.

Natural or hydroxylated jojoba oil / wax derivatives can be obtained by transesterification of said oils / waxes with alcohols having a UV absorbing group, and are presented by the general formulas

CH3 (CH2) nCH = CH (CH2) mCOOR or CH3 (CH2) iCOOR in which R is an organic radical having a UV absorbing group.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 shows the amount (in percentages) of the OMC and di (4methoxycinnamoyl) jojobadiol, which remains in the skin tissue after immersion in water and drying. Figure 2 shows the amount (in percentages) of the OMC and tetra (4methoxycinnamoyl) jojobatetraol, which remains in the skin tissue after immersion in water and drying. Figure 3 shows the WTO standard curve (octyl methoxycinnamate) detected by the HPLC procedure for OMC. Figure 4 shows the standard curve of di (4-methoxycinnamoyl) jojobadiol detected by the HPLC method for di (4-methoxycinnamoyl) jojobadiol. Figure 5 shows the standard curve of OMC (Octyl Methoxy Cinnamate) detected by the HPLC method of di (4-methoxycinnamoyl) jojobadiol. Figure 6 shows the penetration profiles of OMC and di (4methoxycinnamoyl) jojobadiol through the skin. Figure 7 shows the skin accumulation profiles of OMC and di (4methoxycinnamoyl) jojobadiol.

DESCRIPTION OF DETAILED EMBODIMENTS

It is known in this technique that light radiation having wavelengths between 280 nm and 400 nm allows tanning of the human epidermis, and that light radiation having wavelengths between 280 and 320 nm, known as UV-B radiation causes skin burns and erythema, which can be harmful to the development of a natural tan; therefore, this UV-B radiation should seep from the skin. It is also known in this technique that it is likely that UV-A radiation, which has wavelengths between 320 nm and 400 nm, and that causes the skin to tan, induces an adverse change in it, especially in the case of sensitive skin or skin that is continuously exposed to solar radiation. UV-A radiation causes, in particular, a loss of skin elasticity and the appearance of wrinkles, resulting in premature skin aging. UV-A radiation promotes the triggering of the erythemal reaction or amplifies this reaction in certain individuals and may even be the cause of phototoxic or photoallergic reactions. Therefore, it is also desirable to filter the UV-A radiation. Many cosmetic compositions suitable for skin photoprotection (UV-A and UV-B) are known in this technique.

Natural jojoba wax / oil,

CH3 (CH2) 7CH = CH (CH2) mCOO (CH2) nCH = CH (CH2) 7CH3, can be converted into light absorbing substances and used as skin photoprotectors, by hydroxylation and additional esterification with carboxylic acids or amino acids that have UV absorbing groups or by transesterification of said wax / oil or its derivatives hydrogenated with alcohols having UV absorbing groups.

The term "esterification" or "esterified", hereinafter, refers to a process in which carboxylic acids react with alcohols to produce a compound called ester.

By the term "oil" is meant a compound that is liquid at room temperature. By the term "wax" is meant a compound that is solid, or more or less solid, or in another embodiment is liquid, at room temperature.

The term "jojoba wax / oil" also includes jojoba derivatives or substituted compounds.

"Jojoba oil" is an ester of liquid wax, which naturally has a golden color and is found in the seed of the jojoba plant. Jojoba oil is mainly composed of 40 and 42 carbon chain esters, which in turn are composed of monounsaturated fatty acids and fatty alcohols with a chain length of 20 and 22 carbons. Jojoba oil contains less than 3% triglycerides and is very resistant to oxidation. The main use of jojoba oil is for cosmetic purposes, such as skin softening, skin penetration and emolliency.

"Hydrogenated jojoba oil" is a hard, crystalline wax ester created by the complete addition of pressurized hydrogen gas to all points of unsaturation within jojoba oil. The melting point of hydrogenated jojoba oil is 68-70 ° C and the iodine value is <2.0, making it one of the most exceptional high melting wax esters of natural origin available in the market. Hydrogenated jojoba oil is relatively colorless, odorless and has a particular functionality in cosmetic formulations such as lipsticks, masks, eyeliner, lip balm and formulas

Similar.

"Partially hydrogenated jojoba oil" is a semi-soft to hard product that is produced as a result of the incomplete addition of hydrogen to the unsaturation points of jojoba oil. Partially hydrogenated jojoba oil is manufactured through a process known as "selective" or "controlled" hydrogenation or saturation. Partially hydrogenated jojoba oil (as with any partially hydrogenated vegetable oil) contains trans isomers, which have been shown to decrease normal skin metabolism.

"Jojoba esters" is a complex mixture of esters produced by the transesterification of jojoba oil, hydrogenated jojoba oil, or a mixture of both with organic alcohols. Jojoba esters are produced in a wide range of melting points and are colorless, odorless and extremely resistant to oxidative degradation. Jojoba esters are useful as components of highly pigmented cosmetic systems.

The transisomerized jojoba oil is a jojoba oil that has undergone partial or complete transisomerization of its cis double bonds to form trans double bonds, and a very viscous product with a higher melting point. This jojoba oil derivative known as jojoba butter or "Jojobutter" contains approximately 50% trans isomers.

A photoprotective compound for topical application may comprise hydroxylated derivatives of natural jojoba wax / oil or its synthetic substitute, esterified with carboxylic acids or amino acids having UV absorbing groups. The term "photoprotector", earlier herein, refers to a compound or a composition that is applied to the skin to prevent injuries from UV light.

A tanning compound for topical application may comprise hydroxylated derivatives of natural jojoba wax / oil or its synthetic substitute, esterified with carboxylic acids or amino acids for tanning.

The term "tanning compound", earlier herein, refers to a compound that enhances tanning, that is, darkening of skin color, for example, by exposure to the sun.

The term "topical application", earlier herein, refers to the application of substances to the skin or tissue, for example, by extending them. Compositions for topical application are normally in the form of oily solutions, bars, lotions, creams, suspensions, spray aerosols, films, microcapsules, microspheres, liposomes, vesicles, emulsions, microemulsions, lipospheres, patches, solutions,

Etosomes, ethanolic solutions and alcoholic solutions.

Said substances can be prepared by hydroxylation of the ethylenic bonds of the wax / jojoba oil and subsequently esterification with organic acids containing light absorbing groups in the UV region or by transesterification of natural or hydrogenated wax / jojoba oil with alcohols containing groups UV absorbers Although jojoba wax / oil derivatization has been studied extensively in the past (see "Products from Jojoba: A Promising New Crop for Arid Lands", Committee on Jojoba Utilization, Natl. Res. Council, 1975; Johnson, Himman, Science 208,460,1980) only a few attempts to hydroxylate the wax / oil have been reported.

In particular, no attempt to convert the jojoba wax / oil into dihydroxy derivatives (jojobadiols) has been described in the literature, but jojobatetraols were prepared by epoxidation of natural jojoba wax / oil with hydrogen peroxide in acetic acid in the presence of tetrabutylammonium bromide and subsequent hydrolytic cleavage of diepoxide (Shani A., Ind. Eng. Chem. Prod. Res. Deve. 22, 121-123, 1983). A similar procedure was used that involves epoxidation with m-chloroperbenzoic acid and subsequent cleavage of diepoxide in boiling petroleum ether - 20% HCl to tetrahydroxylate the unnatural trans-trans isomer of jojoba wax / oil (Shani A. Ind Eng. Chem. Prod. Res. Dev. 25,78-82, 1986). However, these procedures suffer several defects. In particular, they are accompanied by the formation of considerable quantities of unwanted by-products.

In one embodiment, the invention relates to a compound that is produced as a result of the hydroxylation steps followed by esterification that is represented by the general formula (I)

CH3 (CH2) mCH (OX) (CH2) nCOOH (CH2) iCH (OX) (CH2) kCH3 in which X is an organic light absorbing group in the ultraviolet region and (CH2) i, (CH2) k, ( CH2) my (CH2) n are aliphatic chains containing from 5 to 30 methylene groups. These may be in the form of oily wax / oil esters isolated from the seeds of Simmondsia chinensis and S. californica Nutt. or Buxaceae desert shrub hereinafter referred to as "jojoba wax / oil".

In another embodiment, the invention relates to a compound represented by the general formula (II)

CH3 (CH2) mCH (OX) CH (OX) (CH2) nCOO (CH2) iCH (OX) CH (OX) (CH2) kCH3 in which X is an organic light absorbing organic group in the ultraviolet or tanning region and (CH2) i, (CH2) k, (CH2) m and (CH2) n are aliphatic chains containing 5 to 30 methylene groups.

Other compounds can be represented by the general formulas:

CH3CH = CH (CH) nCOOR or CH3 (CH2) mCOOR

in which R is the rest of an alcohol that has a UV absorber group.

As shown in the Examples section, it was shown that the above esterified compounds reduce the permeability of the skin. Therefore, the compound of the invention prevents or prevents the penetration of small molecules through the skin. The term "penetrate" or "penetration", earlier herein, refers to the introduction of the molecule into the skin layer, where penetration refers to the process of transfer of the molecule and its absorption into the systemic system. Figure 6 shows that the OMC penetrates the skin, while the derivative di (4-methoxycinnamoyl) jojobadiol, no. Figure 7 clearly shows that the WTO accumulates in larger amounts in the skin, and the amount of di (4-methoxycinnamoyl) jojobadiol accumulated in the skin is approximately one third of the amount of the WTO.

In addition, after immersing in water, it has been shown that the amounts of di (4-methoxycinnamoyl) jojobadiol and tetra (4-methoxycinnamoyl) jojobatetraol on the skin after immersion in water were much greater than the amount of the WTO (see examples 3 and 4). Therefore, the compound of the invention is also water resistant.

An oxyercuration method can be used for the monohydroxylation of double bonds and peroxidation of H2O2 catalyzed with osmium tetraoxide with subsequent acid hydrolysis for the dihydroxylation of the ethylenic bonds of the wax / jojoba oil.

Treatment of jojobadiol and jojobatetraol obtained in this manner with p-methoxycinnamoyl chloride and pyridine produced the corresponding esters, di (4-methoxycinnamoyl) jojobadiol (DMJD) and tetra (4-methoxycinnamoyl) jojobatetraol (TMJT) which proved to be effective UV filters. This procedure proved to have three main advantages: (1) the reactions do not affect the wax / jojoba oil ester group; (2) provide the hydroxylated end products with high yields and (3) the complete conversion of the wax / oil into di- or tetraols can be carried out in the form of a "one-step" process, that is, without isolation or purification of the intermediates

When applied to the skin, formulations containing these esters proved to be several times more water resistant than the most commonly used octyl methoxycinnamate.

Natural jojoba wax / oil can be converted into jojobatetraol (see formula II, X = H) by osmium tetraoxide catalyzed peroxidation of cis cis ethylenic bonds and subsequent acid hydrolysis under controlled conditions.

Jojobadiol (formula I, X = H) and jojobatetraol (formula II, X = H) can be esterified

with N-and O-protected aromatic amino acids N-t-Boc-tryptophan and N-t-Boc-O-benzyl tyrosine, with subsequent removal of the protective group to produce the corresponding esters containing two or four amino acid residues attached to the jojoba oil structure.

Jojobadiol (formula I, X = H) and jojobatetraol (formula II, X = H) can be esterified with melanin precursors, such as carboxylated derivatives of dopachrome red or O-protected leucodopachrome, to produce the corresponding esters containing two or four remains of the melanin precursors mentioned above attached to the jojoba wax / oil structure.

Similarly, esterification of jojobadiol and jojobatetraol with tryptophan and tyrosine protected aromatic amino acids (Nt-Boc-tryptophan and Nn-t-Boc-O-benzyl tyrosine) and subsequent elimination of t-Boc protecting groups result in the formation of the corresponding amino acid esters that respectively have two or four tryptophan or tyrosine bound to the wax / jojoba oil structure. An important additional advantage of tryptophan and tyrosine jojoba wax / oil photoprotective derivatives is that in addition to serving as UV filters, these amino acid residues also show a photocitoprotective activity. In addition, tyrosine is the precursor of melanin, a natural sunscreen and photoprotective agent.

Examples of esterifying agents are, without limitation, UVA absorbers, UVB,

UVA + UVB:

benzophenone-4 (acid 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid), acid

aminoantraquinone-2-carboxylic acid,

acid para-amino-benzoic acid, aminopterin, acid

anisilbenzoic, arylocolic acid (natural or synthetic).

Other examples are: alminoprofen, amfenac, p-aminohipuric acid, paminosalicylic acid, p-anisic acid, o- (p-anisoyl) benzoic acid, aspartame, aspirin, caffeic acid, 9-carbazoleacetic acid, carprofen, cinoxacin, citrodisalyl, clobuzarit , clofibric acid, clopirac, diphenic acid, ethacrynic acid, fenclorac, fenoprofen, flurbiprofen, N- (phydroxyphenyl) glycine, indolacitic acid, lobenzarit, menbuton, 3- (o-methoxyphenyl) -2phenylacrylic acid, naproxen, nicotinic acid Sodium phenolphthalein, phenolphthalin, N-phenylantranilic acid, A-phenylcinamic acid, phthalsulfacetamide, phthalsulfatiazole, phytochlorine, piperic acid, pranoprofen, 8-quinolinecarboxylic acid, rosoxacin, salicylic acid, salsalate, O-thymotic acid, 2- timotic acid toluyl) benzoic.

In a further aspect, the present invention provides a photoprotective composition. The photoprotective compositions may comprise a compound comprised of hydroxylated wax derivatives of natural jojoba oil or its synthetic substitute, esterified with carboxylic acids or amino acids having UV absorber groups and one or more additional components selected from the group consisting of additional emollients , skin moisturizers, skin brush accelerators, antioxidants, emulsion stabilizers, thickening agents, moisture retention agents, film formers, preservatives, perfumes and dyes. The composition may contain an oil phase that may comprise any oil conventionally used in cosmetic formulations, especially an emollient, for example, one or more of a fatty alcohol; hydrocarbon oil; a natural or synthetic triglyceride; a wax / oil that includes esters of long chain acids and alcohols as well as compounds having wax / oil properties; a silicone oil; an ester of fatty acid or a fatty alcohol; and products containing lanolin.

Examples of fatty alcohols include cetyl alcohol, stearyl alcohol, octiidodecanol, cetearyl alcohol and oleic alcohol; Examples of hydrocarbon oils are, for example, mineral oil (light or heavy), petrolatum (yellow or white), polyethylene, paraffin, squalane, microcrystalline wax / oil, ceresin, polybutene and hydrogenated polyisobutene; Examples of a natural or synthetic triglyceride include castor oil, caprylic / capric triglyceride, Japan wax, hydrogenated vegetable oil, sweet almond oil, wheat germ oil, sesame oil, hydrogenated cottonseed oil, coconut, wheat germ glycerides, avocado oil, corn oil, trilaurin, hydrogenated castor oil, shea butter, cocoa butter, soybean oil, mink oil, sunflower oil, cartam oil, oil of macadamia nut, olive oil, hydrogenated tallow, apricot oil, hazelnut oil and boraja oil; Examples of a wax include esters of long-chain acids and alcohols, as well as compounds that have wax-like properties, for example, carnaúba wax, beeswax (white or yellow), lanolin, candelellila wax, ozoquerite, oil lanolin, paraffin, Japan wax, microcrystalline wax, ceresin, jojoba oil, cetayl ester wax, synthetic jojoba oil, synthetic beeswax and lanolin wax; a silicone oil is, for example, dimethicone or cyclomethicone; Examples of a fatty acid ester or a fatty alcohol include isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, C12-C15 alcohol benzoate, cetearyl octanoate, cetyl palmitate, Myristyl myristate, myristyl lactate, cetyl acetate, dicaprilat / propylene glycol caprate, decyl oleate, acetylated lanolin, stearyl heptanoate, diisoestearyl malate, octyl hydroxystearate, octyl hydroxystearate and isopropyl isostearate; and examples of products containing lanolin include lanolin, lanolin oil, isopropyl lanolate, acetylated lanolin alcohol, acetylated lanolin, hydroxylated lanolin, hydrogenated lanolin and lanolin wax.

The emulsifier may comprise any emulsifier conventionally used.

in cosmetic formulations, for example, one or more of an ethoxylated ester of a natural oil derivative such as a polyethoxylated ester of hydrogenated castor oil; a silicone oil emulsifier such as a silicone polyol; an optionally ethoxylated fatty acid soap; an ethoxylated fatty alcohol; an optionally ethoxylated sorbitan ester; an ethoxylated fatty acid; or an ethoxylated glyceride.

The composition of the invention may also comprise other components that are known to perform a useful function in a sunscreen composition. Examples of such additional components include, for example, emollients, skin moisturizers, skin tanning accelerators, antioxidants, emulsion stabilizers, thickening agents such as xanthan, moisture retention agents such as glycerin, film formers , preservatives, perfumes and dyes.

The compound of the invention as defined by the general formulas (I) and (II) can be formulated in any cosmetic preparation that is specially designed to be water resistant. The total level of compound of the invention in these preparations will typically be of the order of about 0.5 to 60%, by weight, and in another embodiment within the range of about 5-30%, by weight. It is contemplated that the agents of the present invention will be incorporated into formulations that are effective and safe. An effective amount (or photoprotective amount) is the amount that is sufficient to induce a significantly positive effect of protection against UV sunlight, compared to a control. A safe amount is one that does not produce serious side effects.

The composition may be in the form of oily solutions, bars, lotions, creams, suspensions, spray aerosols, films, microcapsules, microspheres, liposomes, vesicles, emulsions, microemulsions, lipospheres, patches, solutions, ethosomes, ethanolic solutions and alcoholic solutions. The basis of the formulation may be a water-in-oil emulsion, an oil-in-water emulsion, an alcohol-in-oil alcohol lotion, a vesicular dispersion, or be in the form of a starch / lipid dispersion without emulsifiers as described in U.S. Patent Nos. 5,676,994 and 5,882,713. The term "oil", as used herein. It includes all lipids. The term "lipid" (or fat) is a global term that refers to substances found in living cells and that are composed solely of a non-polar hydrocarbon residue or a hydrocarbon residue with polar functional groups (see Encyclopedia of Chemistry, 3rd edition, CA Hampel and GG Hawley, eds., 1973, page 632. Most lipids are insoluble in water and are soluble in fatty solvents such as ether and chloroform.

Other components that can be included in sunscreen formulations include: others

UVA and UVB sunscreen agents, such as 2-phenyl-benzimidazol-5-sulfonic acid, TEA salicylate, octyl dimethyl PABA, padimato-O (4- (dimethylamino) 2-ethylhexyl benzoate) and octyl methylcinamate; inorganic physical sun blockers, such as zinc oxide and TiO2; artificial tanning agents; abrasives; absorbents; fragrances; pigments; dyes / dyes; essential oils; skin sensitizers; excipients and astringent vehicles; thickening / structuring agents; emollients; emulsion stabilizers; excipients and auxiliaries usually incorporated in cosmetic formulations; humectants; moisturizers; skin conditioners; anti-caking agents; antifoaming agents; antimicrobial agents; antioxidants; binders; buffering agents; loading agents; chelating agents; chemical additives; film formers; humectants; opacifying agents; skin conditioning agents; vitamins; and the like

As previously indicated, the compositions of the invention are useful as sunscreen agents to provide protection against the adverse effects of UV radiation. The main application is in the form of a topical sunburn protector for human skin. However, it is anticipated that the compositions and formulations of the invention will also have veterinary applications as a skin protector. The sunscreen formulations contemplated herein can be applied to the skin by spreading or spraying a thin layer thereof on the surface of the skin to be protected.

Resins, when used, include, but are not limited to, aromatic / aliphatic resins, hydrogenated aromatic resins, polyterpene, synthetic resins (including hydrogenated pentaerythrityl rosinate), rosin, acrylics, silicones and other resins (including polyol prepolymers and LEXOREZ resins 100, marketed by Inolex Corporation).

The gelling agents include, but are not limited to, clays (including stearalkonium hectorite, quaternium-18 bentonite and quaternium-18 hectorite) and metal soaps (including aluminum and zinc stearates).

The dyes and pearlescent preferably include a classic raw material without any surface treatment. Charges include, but are not limited to, mica, talc and sericite. Functional charges include, but are not limited to, spherical particles (including PMMA, silica, nylon and microbubbles), boron nitride, starches, silica, lauroyl-lysine and Teflon.

Wetting agents include, but are not limited to, low HLB emulsifiers, polyglyceryl esters (including polyglyceryl 3-diiso stearate), hydrogenated lecithin, lanolin alcohols, polyhydroxystearic acid and soy sterols.

The texturizing agents on an anhydrous base of the invention are preferably surface treated. Texturing agents include, but are not limited to, nylon, PMMA, serecita, talc, mica, boron nitride, Teflon, microbubbles (including glass and polyvinylidene), spherical silica, starches (including oats, rice, wheat and corn), oxychloride Bismuth, microcrystalline cellulose, polyurethane powder and silicone powder.

Preferably, the pigments are surface treated and include, but are not limited to, titanium dioxide (including pigmentary and ultrafine), zinc oxide (including pigmentary and ultrafine) and iron oxides (including pigmentary and ultrafine).

In these embodiments, surface treated raw materials are preferred to improve dispersibility and enhance solid loads to provide a drier texture, create a matte appearance and improve use.

Cosmetic compositions may include pressed face powders, loose face powders, pressed face base, blusher, eyeshadow, anhydrous base, anhydrous mask, anhydrous eye shadow, bright classic lipstick, classic lipstick Matte and volatile lipstick, which generally include from about 0.01% by weight to about 20% by weight of a compound of formula (I) or (II).

The compound of the invention can be used in the preparation for the treatment of skin conditions selected from the group consisting of acne, psoriasis, seborrheic dermatitis, dandruff, warts, corns, hardness, ringworm infection, wrinkles, yellowing, hardness, marbled e hyperpigmentation The presence of the compound of the invention will prevent the penetration of the compositions to treat these conditions in deeper layers of the skin and prevent their washing with water.

When used as a treatment for skin conditions, a compound of formula (I) will preferably be released in a safe and effective amount. The term "safe and effective amount" is defined as any amount sufficient to induce a positive modification in the condition to be treated, but low enough to avoid serious side effects (in a reasonable benefit / risk ratio) within the scope of medical judgment. The safe and effective amount of the compounds of formula (I) will vary with the particular condition being treated, the age and physical condition of the patient being treated, the severity of the condition, the duration of treatment, the nature of concurrent therapy. , the specific compound or compounds of the invention used, the particular vehicle used, if any, and similar factors in the knowledge and experience of the physician. EXAMPLES Example 1 Preparation of di (4-methoxycinnamoyl) jojobadiol

A solution of 12.12 g of wax / jojoba oil (approx. 0.02 mol) in 80 ml of tetrahydrofuran is added to 12.74 g (0.04 mol) of mercury acetate in 20 ml of water and 0 , 1 ml of acetic acid and the mixture is stirred for 6.5 h in a closed vessel in a hydrogen atmosphere, the course of the reaction being followed by TLC. After this, sodium borohydride (0.7 g) in 40 ml of 1.5 M NaOH is added in small portions with constant stirring so that the temperature of the reaction mixture never exceeds 30 ° C and stirring is continued for 2 hours. After the mercury settles, the aqueous phase is saturated with NaCl, the phases are separated and the tetrahydrofuran is removed from the upper phase by distillation. The residue is dissolved in 60 ml of chloroform and washed three times with 40 ml of a saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The jojobadiol oil, 10.86 g (84.6%), solidifies after a period of rest at room temperature, forming colorless crystals of the erythro isomer, m.p. 86-88 ° C. IR (pure): 3300-3400, 1750 cm 1H NMR: 4.8-4.9 (2 H, OH, sa), 3.96-4.00 (triplet, -CH2OCO), 3.6 (2H, CHOH), 2.20-2.26 (triplet, CH2COO), 1.2-1.4 (aliphatic hydrogens), 0.92-0.94 (triplet, CH3).

A solution of 4.0 g (approx. 6.2 mmol) of jojobadiol (mixture of threo and erythro forms) in 60 ml of chloroform containing 1 g (13 mmol) of pyridine is added dropwise with constant stirring at temperature ambient to a solution of 2.48 g (13 mmol) of 4-methoxycinnamoyl chloride in 40 ml of chloroform. Stirring is continued for 1 hour and the mixture is washed consecutively with water, dilute HCl, water, 10% aqueous NaOH and water and dried over anhydrous sodium sulfate. The solution is concentrated and the residue is purified by column chromatography on silica gel 60 using as eluent a mixture of diethyl ether-petroleum ether (1: 9, v / v). Di (4-methoxycinnamoyl) jojobadiol is obtained in the form of a colorless viscous liquid. Yield 3.1 g (48.4%). IR: 1725, 1620, 1602, 1580, 1520 cm. 1H NMR: 7.7 (2H, CH = CH, d), 7.47-7.50 (4H, C6H4), 6.3 (2H, CH = CH), 3096-4.00 (triplet, CH2OCO) , 3.80 (6H, OCH3, s), 3.76 (2H, CHOCO, m), 2.16 (triplet, -CH2COO), 1.2-1.4, aliphatic hydrogens). UV: max 290 nm. Example 2 Preparation of Tetra (4-methoxycinnamoyl) jojobatetraol

Osmium tetraoxide (1 g) is dissolved in 200 ml of diethyl ether. 1 ml of that solution is added to a solution of 12.12 g (approx. 0.02 mol) of jojoba wax / oil in 20 ml of acetone and 40 ml of diethyl ether. 6 ml of 30% hydrogen peroxide is added dropwise to the last solution with constant stirring so that the reaction temperature never exceeds 30 ° C. The mixture is stirred for 8 hours at room temperature and concentrated in vacuo. The residual viscous oil is dissolved in 40 ml of petroleum ether and gently heated to the boiling point with 40 ml of 20% hydrochloric acid. The course of the reaction is followed by TLC. After heating under reflux for 4.5 hours and the mixture is cooled to room temperature, the phases are separated, the upper phase is washed three times with 40 ml of saturated NaCl and then dried over anhydrous sodium sulfate. Evaporation under reduced pressure gives 10.5 g (yield 78.1%) of jojobatetraol in the form of a very viscous colorless oil comprising a mixture of erythro isomers (main component) and threo. IR (pure): wide singles at 3300-3400, 1700 cm. The 1H NMR spectrum showed signals in the

5 regions 3.75 (4 H, -CHOH, m) and 3.45 (H, -CHOH) corresponding, respectively, to the erythro and threo forms in a proportion of approx. 4: 1.

The esterification of jojobatetraol (4 g, 5.9 mmol) with 4.64 g (23.6 mmol) of p-methoxycinnamoyl chloride and 2 g of pyridine was performed under the conditions described above for the diol. Tetra (4-methoxycinnamoyl) jojobatetraol (94.4% yield) was obtained as a

10 viscous liquid of slightly yellow color. UV: max 291 nm; 1 g 5.02 (calculated for the average PM). The 1H NMR spectrum coincided with that of the jojobadiol ester dimethoxycinmoyl ester shown above, differing in a higher integral intensity from the corresponding proton signals.

Example 3 Substance of di (4-methoxycinnamoyl) jojobadiol

The objective of the experiment was to compare the substantivity of the derivative DI of OMC against OMC (the term "OMC", earlier herein, refers to octyl methoxycinnamate). An experiment was performed by applying a formulation containing the new derivative to the skin of nude mice and then the skin was submerged in water and

20 dried consecutively 2 times. The immersion time was 20 minutes each time and the drying period was 15 minutes. A formulation containing OMC was used as a control. Formulations:

1. formula di (4-methoxycinnamoyl) jojobadiol (DI): (5% of der. DI)

25

g propylene glycol 2.5 Ethanol 2.5 brij 52 0.3 30 di (4-methoxycinnamoyl) jojobadiol 0.5 Water 4.2

2. WTO formula: (5% WTO)

g propylene glycol 2.5 Ethanol 2.5 brij 52 0.3 di (4-methoxycinnamoyl) jojobadiol 0.5 Water 4.2

3. Pure WTO

5 The conditions used were the following:

Skin: frozen nude mice 7-9 weeks,

male

tºC: room temperature

Solvent medium: Distilled water

Amount of formula on the skin: 5 mg

Skin surface: 6.4 mm2

Skin extracts: 10 ml of EtOH

Experimental results

The amount of the remaining derivatives on the skin after this operation is

10 provided in Fig. 1. It can be clearly seen that the amount of di (4-methoxycinnamoyl) jojobadiol that remained afterwards in the skin was much greater (approximately 80%) than the amount of WTO remaining in the skin, which was of approximately 50%

Example 4 Substance of tetra (4-methoxycinnamoyl) jojobatetraol (TETRA)

The objective of the experiment was to compare the substantivity of the WTO TETRA derivative against the WTO. An experiment was performed applying a formulation containing the new derivative to the skin of nude mice and then the skin was submerged in water and dried consecutively 2 times. The immersion time was 20 minutes each time and the period of

20 drying was 15 minutes. A formulation containing OMC was used as a control.

Formulations:

2. Tetra (4-methoxycinnamoyl) jojobatetraol formula: (5% TETRA)

g propylene glycol 2.5 Ethanol 2.5 brij 52 0.3 tetra (4-methoxycinnamoyl) jojobatetraol 0.5 Water 4.2

2. WTO formula: (5% WTO)

5

g propylene glycol 2.5 Ethanol 2.5 brij 52 0.3 OMC 0.5 Water 4.2

3. Pure WTO

The conditions used were the following:

Skin: frozen nude mice 7-9 weeks,

male tºC: room temperature Solvent medium: Distilled water Amount of formula on the skin: 5 mg Skin surface: 6.4 mm2 Skin extracts: 10 ml of EtOH

10

Experimental results

The amount of the remaining derivatives on the skin after immersion in water and drying is provided in Fig. 1. It can be clearly seen that the amount of Tetra (4-methoxycinnamoyl) jojobatetraol 15 that remained after the skin was much greater ( approximately 90%) than the

amount of OMC that was left on the skin, which was approximately 30%.

Example 5 Measurement of skin penetration of Di (4-methoxycinnamoyl) jojobadiol compared to OMC

The penetration of pure OMC and di (4-methoxycinnamoyl) jojobadiol (two esterified OH groups) was measured using dorsal skin of 7-week-old male nude mice (CD1, Weizmann Institute, Israel).

The experiments were performed for 24 hours at 37 ° C in Franz diffusion cells. Samples of 200 µl were taken at 1, 2, 4, 6, 8 and 24 hours. 10 mg of each compound was applied to each skin (area-1.77 cm2). The receptor compartment contained EtOH: H2O (1: 1). At the end of the experiment, the skin was cleaned and the skins were extracted with 10 ml of EtOH. The amounts of OMC and di (4-methoxycinnamoyl) jojobadiol derivative were tested by HPLC.

Determination of OMC and derivative di (4-methoxycinnamoyl) jojobadiol by HPLC equipment:

Merck-Hitachi D-7000 interface Merck-Hitachi C-7400 variable UV detector Merck-Hitachi L-7300 column oven Merck-Hitachi L-7200 self-sampler Merck-Hitachi L-7100 pump Merck-Hitachi HSM computerized analysis program.

HPLC conditions:

WTO:

Mobile phase: 12% DDW + 88% methanol

Flow: 1.5 ml / min

Temperature: 35ºC

UV detection wave: 308 nm

Column: LiChrospher 100, RP-18, 5 m, 250 x 4 mm (LiChroCART)

Injection volume: 50 µl

Figure 3 demonstrates the WTO standard curve detected by the HPLC procedure for OMC Derivative Di:

Mobile phase: 100% methanol Flow: 1.5 ml / min. Temperature: 35ºC UV detection wave: 308 nm Column: LiChrospher 100, RP-18, 5 µ, 250 x 4 mm (LiChroCART)

Injection volume: 50 µl The minimum amount of Di (4-methoxycinnamoyl) jojobadiol detected is 800 ng / ml The standard curves for the Di (4-methoxycinnamoyl) jojobadiol derivative and OMC measured by

The HPLC procedure for derivative Di are presented in Figures 4 and 5.

5 Experimental Results

The WTO penetration results from the WTO penetration experiments and Di (4-methoxycinnamoyl) jojobadiol derivative are summarized in Figure 6. The amount of OMC that penetrated the skin at the end of the WTO penetration experiment was 876. ± 235 µg. This amount represents 8.76% of the dose applied to the skin.

10 On the contrary, no penetration of the Di (4-methoxycinnamoyl) jojobadiol derivative was observed through the skin during a 24-hour in vitro penetration experiment (the lowest detectable concentration of the Di (4-methoxycinnamoyl) jojobadiol derivative by analysis HPLC was 0.8 µg / ml).

The amounts of OMC and Di (4-methoxycinnamoyl) jojobadiol derivative accumulated in the skin

15 at the end of the experiment are presented in Figure 7. It can be clearly seen that the accumulation of OMC in the skin was three times greater than that of the Di derivative (2956 ± 807 and 900 ± 359 µg, respectively). In conclusion:

The previous experimental results indicate that although the OMC permeates and penetrates the model skin in relatively high amounts, the Di (4-methoxycinnamoyl) jojobadiol derivative prevents this penetration.

Claims (8)

one.

A compound represented by the general formula (I):

CH3 (CH2) mCH (OX) (CH2) nCOO (CH2) iCH (OX) (CH2) kCH3 in which X is an organic group that absorbs light in the ultraviolet region and (CH2) i, (CH2) k, ( CH2) my (CH2) n are aliphatic chains containing from 5 to 30 methylene groups.

2.

A compound according to claim 1, which is di (4-methoxycincinamoyl) jojobadiol.

3.

A compound represented by the general formula (II):

CH3 (CH2) mCH (OX) CH (OX) (CH2) nCOO (CH2) iCH (OX) CH (OX) (CH2) kCH3 in which X is an organic group that absorbs light in the ultraviolet region and (CH2) i, (CH2) k, (CH2) m and (CH2) n are aliphatic chains containing from 5 to 30 methylene groups.

Four.

A compound according to claim 3, which is tetra (4-methoxycinnamoyl) jojobatetraol.

5.

A compound according to claim 1 or 3, wherein OX is an organic group selected from aminoanthraquinone-2-carboxylate, 4-aminobenzoate, anisylbenzoate, aristolocate, aminopterin, 4-aminohipurate, 4-aminosalicylate, 2- (4anisoyl) benzoate, salicylate, caffeate, 9-carbazolacetate, ethacrynate, 3- (2-methoxyphenyl) -2-phenylacrylate, nicotinate, oxiniacinate, N-phenylantranylate, alpha-phenylcinamate, piperate, 8-quinolinecarboxylate, O-thymotate, benzophenone-4- (2-hydroxy -4-methoxybenzophenone-5-sulfonate) and 2- (p-tolyl) benzoate.

6.

A photoprotective composition comprising the compound according to any one of claims 1 to 5.

7.

A photoprotective composition according to claim 6, comprising one

or more additional components selected from the group consisting of emollients, skin moisturizers, skin tanning accelerators, antioxidants, emulsion stabilizers, thickening agents, moisture retention agents, film formers, preservatives, perfumes and dyes . 8. A composition according to claim 6, wherein said composition is in the form of oily solutions, lotions, creams, suspensions, spray aerosols, films, microcapsules, microspheres, liposomes, vesicles, emulsions, microemulsions, lipospheres, patches , solutions, ethosomes, ethanolic solutions and alcoholic solutions.